Interictal Spikes: Signs of a Negative‐feedback Mechanism of Epilepsy?

Abstract

We read with great interest the article by Massimo Avoli (1), as it summarized recent findings of the Mon-treal group about the effect of interictal epileptiform discharges (IEDs) on seizure generation in the hippocampal formation. The author concluded that the hippocampal IEDs control the ability of the entorhinal cortex to generate seizures. Although data supporting this conclusion have been increasing over the last 15-year period, this fact is usually ignored in clinical practice and in experimental studies, in which IEDs are assumed to represent epileptic activity. This ignorance may lead to false interpretation of human and experimental studies, or even of clinical findings. In a recent study, we examined the relations between IEDs and seizures in another aspect: How do the IEDs relate to the preceding seizure (2)? The frequency of IEDs is highest after seizures, and Gotman and Koffler (3) concluded that IEDs are influenced primarily by the preceding seizures. These data also may suggest that IEDs are induced by seizures. To confirm this hypothesis also requires a spatial relation between seizure and spike localization. Our study was designed to determine whether the localization of interictal spikes depends on the localization of the preceding seizure onset or the seizure propagation (2). The main problem in studying this question is that it is impossible to determine every brain region involved during the seizure, because we are unable to cover the whole brain with intracranial electrodes. Therefore in our study, we chose patients with bitemporal independent IEDs, in whom the localization of seizure activity and IEDs could be simplified to the issue of lateralization. We selected 18 temporal lobe epilepsy (TLE) patients who had bi-temporal independent IEDs to see if the lateralization of IEDs depends on whether the preceding seizure involved one or both temporal lobes. The conclusion of our study is that the lateralization of IEDs is influenced by the lateralization of the onset of a preceding seizure if the seizure activity involves only one hemisphere (p < 0.001). In seizures with contralateral propagation, we did not find a correlation between the localization of seizure onset and the postictal spike distribution. Our findings suggest that the localization of IEDs may depend on the brain areas involved by the preceding seizure, indicating that spikes can be influenced by the seizure activity, and are not independent signs of epileptogenicity (2). The fact that IEDs inhibit the expression of seizures (1), and conversely, that the seizures induce IEDs (2,3), may lead to a hypothesis explaining the role of IEDs in the epileptic brain: IEDs (or rather the underlying neu-rophysiologic processes) represent a negative-feedback mechanism. Figure 1 illustrates this hypothesis. REFERENCES 1. Avoli M. Do interictal discharges promote or control seizures? Experimental evidence from an in vitro model of epileptiform discharge. Epilepsia 2001;42(suppl 3):2-4. 2. Janszky J, Fogarasi A Jokeit H, et al. Spatiotemporal relationship between seizure activity and interictal spikes in temporal lobe epilepsy. Epilepsy Res 2001;47:179-88. 3. Gotman J, Koffler DJ. Interictal spiking increases after seizures but does not after decrease in medication. Electroencephalogr Clin Neurophysiol 1989;72:7-15. 4. Wieser HG. Preictal EEG findings [Abstract]. Epilepsia 1989;30: 664. The Tooth-losing Dream and the Epileptic State To the Editor: The recent case report in Epilepsia by Koutroumanidis et. al. (1) on tooth brushing-induced seizures contributes, perhaps inadvertently, to the understanding of dream-seizure relations. A 28-year-old woman had three generalized convul-FIG. 1. The negative-feedback hypothesis about the role of in-terictal epileptiform discharges in localization-related epilepsy. Seizures exert a positive effect on the production of spikes, resulting in an increase of spike production (3) in the areas involved during the seizures (2). Conversely, these spikes (their underlying neurophysiologic mechanism) inhibit the expression of seizures (1). As spike frequency is usually decreased before seizures (4), this decrease may be a sign of the decrease of the negative-feedback mechanism, which promotes seizures.